Table 2.
Genotype effects on pharmacokinetic parameters after a single oral administration of DA-8031, 5–120 mg
| Pharmacokinetic Parameters | CYP2D6
|
CYP2C19
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EM (N=35) |
IM (N=19) |
P-value | UM (N=1) |
EM (N=20) |
IM (N=22) |
PM (N=11) |
P-value | ||||
| Mean (CV%) |
Mean (CV%) |
GMRa (90% CI) | Mean | Mean (CV%) |
Mean (CV%) |
GMRa (90% CI) |
Mean (CV%) |
GMRa (90% CI) |
|||
| Cmax/dose | 1.1 (32.0) | 1.5 (24.6) | 1.43 (1.23, 1.64) | <0.001 | 1.4 | 1.2 (33.8) | 1.2 (32.2) | 1.02 (0.85, 1.22) | 1.3 (38.3) | 1.04 (0.82, 1.31) | 0.623 |
| AUC0–t/dose | 18.9 (48.1) | 39.1 (38.6) | 2.16 (1.67, 2.78) | <0.001 | 20.1 | 25.2 (58.6) | 25.0 (61.6) | 1.00 (0.72, 1.39) | 30.5 (52.6) | 1.18 (0.77, 1.81) | 0.919 |
| MR of M4 | 0.53 (50.4) | 0.18 (68.0) | 0.30 (0.22, 0.41) | <0.001 | 0.43 | 0.35 (66.9) | 0.45 (59.7) | 1.42 (0.91, 2.2) | 0.41 (97.7) | 1.16 (0.64, 2.10) | 0.247 |
| MR of M5 | 0.60 (70.3) | 0.26 (111.2) | 0.35 (0.24, 0.50) | 0.007 | 0.61 | 0.53 (61.8) | 0.47 (68.5) | 0.36 (0.57, 1.31) | 0.42 (159.7) | 0.53 (0.28, 0.98) | 0.928 |
| MR of M1 | 0.05 (57.8) | 0.09 (18.8) | 2.97 (1.64, 5.26) | <0.001 | 0 | 0.07 (35.3) | 0.07 (46.7) | 0.85 (0.49, 1.48) | 0.05 (55.8) | 0.42 (0.18, 0.96) | <0.001 |
Note:
a
GMRs for IM or PM versus EM.
Abbreviations: CV, coefficient of variation; EM, extensive metabolizer; IM, intermediate metabolizer; UM, ultra-rapid metabolizer; PM, poor metabolizer; GMR, geometric mean ratio; MR, metabolic ratio.